Telomeres research aims to revolutionise hypertension treatment

Hypertension, or high blood pressure, is a worldwide concern and a condition that can lead to severe health problems, making it a preventable leading cause of early death.

Risk factors for this serious health issue include genetics, poor diet, and low physical activity. The World Health Organization (WHO) estimates 1.28 billion adults aged 30–79 have hypertension, but only 21 per cent of people with the condition have it under control.

Federation researcher PhD candidate Arinola Akinnibosun from the Health Innovation and Transformation Centre (HITC), who is studying telomeres and the link in hypertension and chronic kidney disease, in collaboration with the University of Melbourne, was recently awarded the Best Student Investigator award at the Cardiac Society of Australia and New Zealand Annual Scientific Meeting in Adelaide.

"Think of telomeres as the plastic tips on the end of shoelaces, but for our chromosomes. As cells divide, these telomeres get shorter. And in some diseases like high blood pressure, they can shorten even faster," Ms Akinnibosun said.

The telomeres are a source of protection for cells, and as they keep shrinking, the cell eventually dies.

"We have also found that the length of the telomeres can be linked to some diseases. When telomeres are short, they have been linked to hypertension prevalence in some population groups."

When someone consistently presents with blood pressure over 140/90 mmHg (millimetres of mercury), they are considered to have high blood pressure. One way to tackle the problem involves focusing on a crucial blood pressure regulation system known as the renin-angiotensin system (RAS).

To help regulate this system and treat high blood pressure, doctors use medications that act as angiotensin receptor blockers (ARB) or angiotensin converting enzyme inhibitors (ACEi).

Research on rats that naturally develop high blood pressure as they age have shown that giving them ARB or ACEi medicines briefly early in life leads to controlled blood pressure even after they stop taking the medication. This lasting positive effect is known as the 'legacy effect of RAS inhibition'.

"We found in these particular rats that if we treat them with some medications before they become hypertensive, even after stopping the medication, they don't develop hypertension," she said.

"This preliminary discovery is especially promising since these rats are a close model to how hypertension develops genetically in humans. Our research is focused on understanding how this works which is important to translating it to humans.

"Our study found that ACEi, such as perindopril, helps protect the telomeres in the kidneys, which play a key role in regulating blood pressure. Additionally, in the heart, certain genes involved in telomere maintenance were present in different amounts in the rats treated with ARB or ACEi, which could be a factor in the lasting benefits observed."

Living in Nigeria and with a background in pharmaceuticals, Ms Akinnibosun's early research interest was in genomics. She saw significant research in hypertension, but little research on the genomics of hypertension in her home country.

"I thought it was interesting that there was so much research, but we didn't have large clinical trials involving the black population. Given that we know genetics of populations are different, we need to tailor our approach to target these groups — that's what got me interested in genomics and hypertension." Arinola Akinnibosun

She began an online search for experts in these fields and compiled a list of experts from around the world. She identified HITC co-director Professor Fadi Charchar as the researcher she most wanted to work with.

"He was working on the Y-chromosome at the time, another area of genetics and hypertension. I thought, 'Okay, he seems like the person to go to'."

That led to her arrival in Ballarat on a Destination Australia scholarship in February 2020, just before the first COVID lockdown.

"The scholarship really helped me because, as you can imagine, coming when a lockdown just started — I had no access to anything, and just having that support was really helpful," she said.

"And Fadi was checking in and connecting me with different people and groups — it made the situation a lot easier to handle."

Now just weeks from completing her PhD, Ms Akinnibosun says the discovery about telomeres and the legacy effect of RAS inhibition is a chapter in a more extensive research narrative.

"By studying these protective ends of chromosomes and anti-hypertensive medication, our research aims to revolutionise how we predict, understand, and treat hypertension and chronic kidney disease to improve prognosis and overall health outcomes," she said.

"Currently, people can use medications to manage kidney disease and may eventually get a kidney transplant, but there's no real treatment. The hope is that this work will help us better predict the disease and lead into the discovery of new treatment options."

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Kidney gene discovery unlocks door to high blood pressure answers